OTC ANORECTAL DRUGS TFM LISTS PETROLATUM AS CATEGORY I EXTERNAL/INTERNAL PROTECTANT; COMBOS OF UP TO THREE CATEGORY I INGREDIENTS ALLOWED IN TFM

Executive Summary

FDA has classified petrolatum as a Category I protectant ingredient for OTC hemorrhoidal products in its OTC Anorectal Drugs Tentative Final Monograph, scheduled for publication in the Federal Register on Aug. 15. Although petrolatum was reviewed as an anorectal product agent, and not a protectant ingredient by FDA's OTC Hemorrhoidal Drugs Panel, the preamble to the TFM notes: "Petrolatum has been placed in Category I by advisory review panels" as an ophthalmic emollient, anorectal agent, and skin protectant. Consequently, the agency proposed a statement of identity for petrolatum as an "anorectal (hemorrhoidal)/skin protectant." On the other hand, the agency reclassified lanolin alcohols to Category III as anorectal protectant ingredients. The panel had recommended lanolin for Category I, FDA noted, even though it had reviewed no products containing the ingredient. In the TFM's combination policy, the agency proposed Category I status for combinations of Category I ingredients "from up to three different therapeutic categories (except protectants)." The panel had recommended such combinations be placed in Category III until final formulation test demonstrate safety and efficacy. FDA said it is "not requiring formulation testing of either single-ingredient or combination anorectal drug products." Comments noted that a number of combinations of Category I single ingredients were consequently recommended for Category III due to lack of final formulation testing. The TFM lists Whitehall's Preparation H ingredient, live yeast cell, in Category III; however, the preamble notes that FDA is currently reviewing results from clinical trials that could move the ingredient to Category I as a wound-healing agent. "Several comments agreed with the panel's minority report that supports the OTC use of live yeast cell derivative as a wound-healing agent," the agency noted. FDA agreed with the panel members that experiments "suggest a positive influence of live yeast cell derivative on wound healing" and show effects like increased oxygen uptake, tissue growth, and epithelization; however, the agency said "there remains a lack of sufficient data on its effectiveness." FDA did not recommend specific vehicles for vasoconstricting ingredients or support a panel recommendation for final formulation testing. The agency said "anorectal active ingredients may be formulated in any safe and suitable vehicle." The preamble urges that ephedrine sulfate and phenylephrine HCl be formulated in vehicles "appropriate for anorectal use" so that the vasoconstrictors are "properly released." Noting that the OTC Hemorrhoidal Drugs Advisory Panel had "concerns about a need for final formulation testing to support safety and effectiveness" and recommended the vasoconstrictors only in aqueous solution, FDA said it "is not proposing the panel's recommendation for final formulation testing." Hydrocortisone was not added to the list of OTC anorectal ingredients, FDA said. Noting that the OTC External Analgesic Drugs TFM, published in 1983, included a label claim for "external anal itching" for hydrocortisone products, the preamble states that hydrocortisone-containing drugs will remain in a single (the external analgesics) rulemaking with the proposed label and not be repeated in the anorectal category. The agency added that the External Analgesics TFM will be amended to require that hydrocortisone products labeled for external anal itching "also be labeled with appropriate general warnings and directions consistent with other OTC anorectal drug products." FDA disagreed with a comment that local anesthetics should be Category I ingredients for intrarectal use, instead of Category III. The preamble notes that the OTC Anorectal Drugs Advisory Panel concluded that "certain local anesthetics, i.e., benzocaine, benzyl alcohol, dyclonine, and pramoxine, could be used safely intrarectally but that data were still needed to establish effectiveness." However, the preamble continues, "this decision does not affect the external use of these ingredients," which were included in the TFM "with appropriate labeling for external use only." Chart omitted.